Ethylmorphine O-deethylation in isolated rat hepatocytes. Involvement of codeine O-demethylation enzyme systems.

@article{Xu1995EthylmorphineOI,
  title={Ethylmorphine O-deethylation in isolated rat hepatocytes. Involvement of codeine O-demethylation enzyme systems.},
  author={B. Q. Xu and T A Aasmundstad and Anders Bj{\o}rneboe and Asbj{\o}rg Solberg Christophersen and J{\o}rg Gustav M{\o}rland},
  journal={Biochemical pharmacology},
  year={1995},
  volume={49 4},
  pages={
          453-60
        }
}
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22 Citations
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22 Citations

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Evidence for CYP2D1-mediated primary and secondary O-dealkylation of ethylmorphine and codeine in rat liver microsomes.
Effects of ethanol on ethylmorphine metabolism in isolated rat hepatocytes: characterization by means of a multicompartmental model.
TLDR
It was concluded that all steps in the metabolism of ethylmorphine (and codeine) leading to the end products morphine-3-glucuronide and normorphine- 3-glUCuronide were inhibited by ethanol, and that the glucuronidation process were the ones most affected by ethanol.
Demethylation of radiolabelled dextromethorphan in rat microsomes and intact hepatocytes.
TLDR
Compared the inhibitory potencies of a series of CYP2D inhibitors in rat liver microsomes and hepatocytes, the cell-associated concentrations of quinine and quinidine were found to be significantly higher than those in the extracellular medium, suggesting that intracellular accumulation may potentiate the effect of these compounds.
Effect of mirtazapine on the CYP2D activity in the primary culture of rat hepatocytes.
TLDR
The obtained results indicate that mirtazapine applied at pharmacological concentrations can moderately increase the activity of rat CYP2D in hepatocytes, and CYP 2D2 isoform contributes mostly to this effect.
Cytochrome P450 isoenzymes involved in rat liver microsomal metabolism of californine and protopine.
Inhibition of rat liver CYP2D in vitro and after 1-day and long-term exposure to neuroleptics in vivo–possible involvement of different mechanisms
Comparative biotransformation of morphine, codeine and pholcodine in rat hepatocytes: identification of a novel metabolite of pholcodine
TLDR
The hypothesis that the absence of analgesic activity with pholcodine may be due to less O -dealkylation in vivo is supported and its antitussive efficacy is suggested to be mediated by the parent drug or one of its metabolites other than morphine.
First demonstration that brain CYP2D-mediated opiate metabolic activation alters analgesia in vivo.
Centrally administered CYP2D inhibitors increase oral tramadol analgesia in rats
Nicotine Increases Codeine Analgesia Through the Induction of Brain CYP2D and Central Activation of Codeine to Morphine
TLDR
It is shown that brain CYP2D alters drug response despite the presence of substantial first-pass metabolism of codeine and further that nicotine induction of brain CYp2D increases codeine response in vivo.
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References

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Codeine O-demethylation: rat strain differences and the effects of inhibitors.
Thebaine O-demethylation to oripavine: genetic differences between two rat strains.
TLDR
Thebaine O-demethylation was inhibited by quinine and known substrates of cytochrome P 450 IID1/P450 IID6, supporting the major involvement of cy tochrome P450 I ID1 in oripavine formation in rats.
Primary and secondary oxidative metabolism of dextromethorphan. In vitro studies with female Sprague-Dawley and Dark Agouti rat liver microsomes.
Simultaneous quantification of ethylmorphine O-deethylase and N-demethylase activity by high-performance liquid chromatography.
Bioactivation of the narcotic drug codeine in human liver is mediated by the polymorphic monooxygenase catalyzing debrisoquine 4-hydroxylation (cytochrome P-450 dbl/bufI).
The kinetics of ethylmorphine N-demethylation in isolated hepatocytes: the effect of drug transport and oxygen concentration.
TLDR
The current study indicates that ethylmorphine is transported into the hepatocyte with a Km of 250 microM and Tm of 20 nmol/min 10(6) cells, and indicates that the effects of oxygen pressure on the kinetic parameters should be considered in predicting in vivo kinetics from in vitro studies.
Polymorphic formation of morphine from codeine in poor and extensive metabolizers of dextromethorphan: Relationship to the presence of immunoidentified cytochrome P‐450IID1
TLDR
The comeasurement of the O‐dem methylation and N‐demethylation of codeine may provide a tool with which to phenotype individuals in vitro with respect to the polymorphism of the cytochrome P‐450IID1.
In-vivo and in-vitro dextromethorphan metabolism in SD and DA rat. An animal model of the debrisoquine-type polymorphic oxidation in man.
Codeine O-demethylation co-segregates with polymorphic debrisoquine hydroxylation.
TLDR
The O-demethylation of codeine to form M appears to be under the same polymorphic genetic control as the 4-hydroxylation of debrisoquine.
Ethylmorphine metabolism in isolated rat hepatocytes.
TLDR
The ratios between the intra-/extra-cellular concentrations of ethylmorphine increased somewhat from an initial value of 4 during the period for which ethyl Morphine could be detected intracellularly, and the drug metabolites all exhibited ratios above 10 for the initial 100 min. of incubation.
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